Evidence map›Paper›PMID 40592886›Full record

ArticleNature communications2025

Generating combinatorial diversity via engineered V(D)J-like recombination in Saccharomyces cerevisiae.

Andrew P Cazier, Jaewoo Son, Sreenivas Yellayi, Lizmarie S Chavez, Caden Young, Olivia M Irvin, Hannah Abraham, Saachi Dalvi, John Blazeck

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Andrew P CazierSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Jaewoo SonSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Sreenivas YellayiSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Lizmarie S ChavezSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Caden YoungSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Olivia M IrvinSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Hannah AbrahamSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Saachi DalviSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
John BlazeckSchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA. john.blazeck@chbe.gatech.edu.ORCID http://orcid.org/0000-0002-6110-2938

Funding

Synthetic metabolism to armor and enhance a new class of cell therapiesDP2CA280622 · NCI · GEORGIA INSTITUTE OF TECHNOLOGY · PI BLAZECK, JOHN JAMES · 2022 to 2025
$2.3M
Arnold and Mabel Beckman Foundation Beckman Young Investigator AwardNCI NIH HHS DP2 CA280622U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) 1DP2CA280622-01
6 · The paper itself

Abstract

V(D)J recombination is integral to the development of antibody diversity and proceeds through a complex DNA cleavage and repair process mediated by several proteins, including recombination-activating genes 1 and 2, RAG1 and RAG2. V(D)J recombination occurs in all jawed vertebrates but is absent from evolutionarily distant relatives, including the yeast Saccharomyces cerevisiae. As yeast grow quickly and are a platform for antibody display, engineering yeast to undergo V(D)J recombination could expand their applicability for studying antibody development. Therefore, in this work we incorporate RAG1 and RAG2 into yeast and characterize the resulting recombination ability using a split antibiotic resistance assay, demonstrating successful homology-assisted formation of coding joints. By pursuing a variety of strategies, we increase the rate of homology-assisted recombination by over 7000-fold, with the best rates approaching 1% recombination after four days. We further show that our platform can assay the severity of several disease-causing RAG1 mutations. Finally, we use our engineered yeast to simultaneously generate up to three unique fluorescent proteins or two distinct antibody fragments starting from an array of nonfunctional gene fragments, which we believe to be the first-ever generation of genetic and phenotypic diversity solely using random recombination of preexisting DNA in a non-vertebrate cell.

Indexed as

Saccharomyces cerevisiaeV(D)J RecombinationDNA-Binding ProteinsGenetic EngineeringHomeodomain ProteinsMutationSaccharomyces cerevisiae ProteinsDNA-Binding ProteinsHomeodomain ProteinsRAG-1 proteinSaccharomyces cerevisiae Proteins

Identifiers

PMID40592886
PMCPMC12216023

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.